Thiophenol → HCID 89389236, compound

HRID 713437Notes

Reaction equation

HRID 713437 reaction equation
[CH:1]1([CH2:4][N:5]([CH2:18][C:19]2[NH:20][C:21](=[O:29])[CH:22]3[CH2:28][O:27][CH2:26][CH2:25][CH:23]3[N:24]=2)[C:6]([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]2)=[O:7])[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[C:39]1([SH:45])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:39]1([S:45][C:15]([CH:12]2[CH2:11][CH2:10][N:9]([CH2:8][C:6](=[O:7])[N:5]([CH2:4][CH:1]3[CH2:2][CH2:3]3)[CH2:18][C:19]3[NH:20][C:21](=[O:29])[CH:22]4[CH2:28][O:27][CH2:26][CH2:25][CH:23]4[N:24]=3)[CH2:14][CH2:13]2)=[O:17])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 7969ThiophenolHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71227223HCID 71227223, compound

Product 1

HCID 89389236HCID 89389236, compoundYield 64.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-{[cyclopropylmethyl-(4-oxo-3,4a,5,7,8,8a-hexahydro-4H-pyrano[4,3-d]pyrimidin-2-ylmethyl)-carbamoyl]-methyl}-piperidine-4-carboxylic acid (0.5 g, 1.24 mmol, 1 eq.) in 5 mL of DMF was added DIEA (0.432 mL, 2.47 mmol, 2 eq.), thiophenol (0.14 mL, 1.36 mmol, 1.1 eq.), followed by HATU (0.517 g, 1.36 mmol, 1.1 eq.) at 0° C. The resulting mixture was allowed to warm to room temperature and stirred overnight. After 18 h, the reaction mixture was concentrated in vacuo to give an oil. This oil was purified by silica gel column chromatography (98/1/1 to 95/4/1 dichloromethane/MeOH/NH4OH) to give the title compound as an orange sticky oil (0.4 g). 1H NMR (400 MHz, chloroform-d) δ ppm 7.48-7.58 (m, 2H), 7.33-7.48 (m, 3H), 4.54-4.64 (m, 2H), 4.48-4.54 (m, 1H), 4.34-4.46 (m, 1H), 3.91-4.06 (m, 2H), 3.23-3.42 (m, 3H), 2.92-3.08 (m, 1H), 2.80-2.89 (m, 1H), 2.54-2.76 (m, 2H), 2.18-2.37 (m, 2H), 1.60-1.84 (m, 6H), 0.92-1.01 (m, 1H), 0.41-0.63 (m, 2H), 0.19-0.35 (m, 2H). Exact mass calculated for C26H33N4O4S1 497.2. MS (ESI) m/z 497.2 (M+H)+ (5-95% CH3CN/H2O over 2 min with 0.1% formic acid, Inertsil 3×3 mm C-8-3 column with flow rate of 2 mL/min).

Workup

  1. waitAfter 18 h
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customto give an oil
  4. customThis oil was purified by silica gel column chromatography (98/1/1 to 95/4/1 dichloromethane/MeOH/NH4OH)

Sources & evidence

ORD record
ord-2cdf6d3f801f46f488b1a7e3f71f019c
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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